tbuckley/cabot-search huggingface dataset:
Impaired T cell IRE1α/XBP1 signaling directs inflammation in experimental heart failure with preserved ejection fraction
Authors: Sasha Smolgovsky, Abraham L. Bayer, Kuljeet Kaur, Erin Sanders, Mark Aronovitz, Mallory E. Filipp, Edward B. Thorp, Gabriele G. Schiattarella, Joseph A. Hill, Robert M. Blanton, Juan R. Cubillos-Ruiz, Pilar Alcaide
Journal: Journal of Clinical Investigation (2023)

Heart failure with preserved ejection fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune pathophysiology. Using a 2-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occurred concomitantly with cardiac pathology and that diastolic dysfunction, cardiomyocyte hypertrophy, and cardiac phospholamban phosphorylation were T cell dependent. Heart-infiltrating T cells were not restricted to cardiac antigens and were uniquely characterized by impaired activation of the inositol-requiring enzyme 1α/X-box-binding protein 1 (IRE1α/XBP1) arm of the unfolded protein response. Notably, selective ablation of XBP1 in T cells enhanced their persistence in the heart and lymphoid organs of mice with preclinical HFpEF. Furthermore, T cell IRE1α/XBP1 activation was restored after withdrawal of the 2 comorbidities inducing HFpEF, resulting in partial improvement of cardiac pathology. Our results demonstrated that diastolic dysfunction and cardiomyocyte hypertrophy in preclinical HFpEF were T cell dependent and that reversible dysregulation of the T cell IRE1α/XBP1 axis was a T cell signature of HFpEF.
Author Correction: Heat-related mortality in Europe during the summer of 2022
Authors: Joan Ballester, Marcos Quijal-Zamorano, Raúl Fernando Méndez Turrubiates, Ferran Pegenaute, François R. Herrmann, Jean Marie Robine, Xavier Basagaña, Cathryn Tonne, Josep M. Antó, Hicham Achebak
Journal: Nature Medicine (2023)

In the version of this article initially published, there was a typographical error in the second paragraph of the Discussion, where in the text now reading "As a reference, a previous study [Epidemiology 34, e5-e6 ( 2023)] applied similar epidemiological models to daily temperature and mortality data for Spain only, and found that the summer heat-related mortality burden was 6% higher (that is, 12,054 deaths) than the one reported here…," 6% originally read "10%" and 12,054 originally read "12,504".The errors have been corrected in the HTML and PDF versions of the article.
Epicardial adipose tissue, metabolic disorders, and cardiovascular diseases: recent advances classified by research methodologies
Authors: Yujie Song, Yanzhen Tan, Meng Deng, Wenju Shan, Wenying Zheng, Bing Zhang, Jun Cui, Lele Feng, Lei Shi, Miao Zhang, Yingying Liu, Yang Sun, Wei Yi
Journal: MedComm (2023)

Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy and physiology of the EAT determines its great potential in locally influencing adjacent tissues such as the myocardium and coronary arteries. Classified by research methodologies, this study reviews the latest research progress on the role of EAT in cardiovascular diseases (CVDs), particularly in patients with metabolic disorders. Studies based on imaging techniques demonstrated that increased EAT amount in patients with metabolic disorders is associated with higher risk of CVDs and increased mortality. Then, in-depth profiling studies indicate that remodeled EAT may serve as a local mediator of the deleterious effects of cardiometabolic conditions and plays a crucial role in CVDs. Further, in vitro coculture studies provided preliminary evidence that the paracrine effect of remodeled EAT on adjacent cardiomyocytes can promote the occurrence and progression of CVDs. Considering the important role of EAT in CVDs, targeting EAT might be a potential strategy to reduce cardiovascular risks. Several interventions have been proved effective in reducing EAT amount. Our review provides valuable insights of the relationship between EAT, metabolic disorders, and CVDs, as well as an overview of the methodological constructs of EAT-related studies.
Methylation of <i>ESR1</i> promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers
Authors: Ji‐Wei Li, Qiu‐Min Deng, Jian‐Ling Zhu, Wei Min, Xiao‐Yi Hu, Hong‐ Yu Chen, Zhong Luo, Lin‐Ling Lin, Xiao‐Long Wei, Yong‐Qu Zhang, Kang‐Liang Lou, Yi‐Yang Gao, Guo‐Jun Zhang, Jing‐Wen Bai
Journal: MedComm (2023)

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα-positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and
Benchmarking algorithms for joint integration of unpaired and paired single-cell RNA-seq and ATAC-seq data
Authors: Michelle Y. Y. Lee, Klaus H. Kaestner, Mingyao Li
Journal: Genome biology (2023)

Single-cell RNA-sequencing (scRNA-seq) measures gene expression in single cells, while single-nucleus ATAC-sequencing (snATAC-seq) quantifies chromatin accessibility in single nuclei. These two data types provide complementary information for deciphering cell types and states. However, when analyzed individually, they sometimes produce conflicting results regarding cell type/state assignment. The power is compromised since the two modalities reflect the same underlying biology. Recently, it has become possible to measure both gene expression and chromatin accessibility from the same nucleus. Such paired data enable the direct modeling of the relationships between the two modalities. Given the availability of the vast amount of single-modality data, it is desirable to integrate the paired and unpaired single-modality datasets to gain a comprehensive view of the cellular complexity.
CRISPR screening in hematology research: from bulk to single-cell level
Authors: Sarah Meyers, Sofie Demeyer, Jan Cools
Journal: Journal of Hematology & Oncology (2023)

The CRISPR genome editing technology has revolutionized the way gene function is studied. Genome editing can be achieved in single genes or for thousands of genes simultaneously in sensitive genetic screens. While conventional genetic screens are limited to bulk measurements of cell behavior, recent developments in single-cell technologies make it possible to combine CRISPR screening with single-cell profiling. In this way, cell behavior and gene expression can be monitored simultaneously, with the additional possibility of including data on chromatin accessibility and protein levels. Moreover, the availability of various Cas proteins leading to inactivation, activation, or other effects on gene function further broadens the scope of such screens. The integration of single-cell multi-omics approaches with CRISPR screening open the path to high-content information on the impact of genetic perturbations at single-cell resolution. Current limitations in cell throughput and data density need to be taken into consideration, but new technologies are rapidly evolving and are likely to easily overcome these limitations. In this review, we discuss the use of bulk CRISPR screening in hematology research, as well as the emergence of single-cell CRISPR screening and its added value to the field.
Author Correction: Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population
Authors: Jonathan J. Lau, Samuel M. S. Cheng, Kathy Leung, Cheuk Kwong Lee, Asmaa Hachim, Leo C. H. Tsang, Kenny W. H. Yam, Sara Chaothai, Kelvin K. H. Kwan, Zacary Y. H. Chai, Tiffany H. K. Lo, Masashi Mori, Chao Wu, Sophie A. Valkenburg, Gaya K. Amarasinghe, Eric H. Y. Lau, David S. C. Hui, Gabriel M. Leung, Malik Peiris, Joseph T. Wu
Journal: Nature Medicine (2023)
Author Correction: Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology
Authors: Dominik Sturm, David Capper, Felipe Andreiuolo, Marco Gessi, Christian Kölsche, Annekathrin Reinhardt, Philipp Sievers, Annika K. Wefers, Azadeh Ebrahimi, Abigail K. Suwala, Gerrit H. Gielen, Martin Sill, Daniel Schrimpf, Damian Stichel, Volker Hovestadt, Bjarne Daenekas, Agata Rode, Stefan Hamelmann, Christopher Previti, Natalie Jäger, Ivo Buchhalter, Mirjam Blattner-Johnson, Barbara C. Jones, Monika Warmuth-Metz, Brigitte Bison, Kerstin Grund, Christian Sutter, Steffen Hirsch, Nicola Dikow, Martin Hasselblatt, Ulrich Schüller, Arend Koch, Nicolas U. Gerber, Christine L. White, Molly K. Buntine, Kathryn Kinross, Elizabeth M. Algar, Jordan R. Hansford, Nicholas G. Gottardo, Martin U. Schuhmann, Ulrich W. Thomale, Pablo Hernáiz Driever, Astrid Gnekow, Olaf Witt, Hermann L. Müller, Gabriele Calaminus, Gudrun Fleischhack, Uwe Kordes, Martin Mynarek, Stefan Rutkowski, Michael C. Frühwald, Christof M. Kramm, Andreas von Deimling, Torsten Pietsch, Felix Sahm, Stefan M. Pfister, David. T. W. Jones
Journal: Nature Medicine (2023)
Targeting eIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer
Authors: Na Zhao, Elena B. Kabotyanski, Alexander B. Saltzman, Anna Malovannaya, Xueying Yuan, Lucas C. Reineke, Nadia Lieu, Yang Gao, Diego A. Pedroza, Sebastian J. Calderon, Alex J. Smith, Clark Hamor, Kazem Safari, Sara Savage, Bing Zhang, Jianling Zhou, Luisa M. Solis, Susan G. Hilsenbeck, Cheng Fan, Charles M. Perou, Jeffrey M. Rosen
Journal: Journal of Clinical Investigation (2023)

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages toward an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 and Fgfr1, and induces an interferon (IFN) response uniformly across models. The induction of an IFN response is partially due to the inhibition of Sox4 translation by zotatifin. A similar induction of IFN-stimulated genes was observed in breast cancer patient biopsies following zotatifin treatment. Surprisingly, zotatifin significantly synergizes with carboplatin to trigger DNA damage and an even heightened IFN response, resulting in T cell-dependent tumor suppression. These studies identified a vulnerability of eIF4A in TNBC, potential pharmacodynamic biomarkers for zotatifin, and provide a rationale for new combination regimens consisting of zotatifin and chemotherapy or immunotherapy as treatments for TNBC.
Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging
Authors: Emma C. Mason, Swapna Menon, Benjamin R. Schneider, Christa F. Gaskill, Maggie M. Dawson, Camille M. Moore, Laura Craig Armstrong, Okyong Cho, Bradley W. Richmond, Jonathan A. Kropski, James D. West, Patrick Geraghty, Brigitte N. Gomperts, Kevin C. Ess, Fabienne Gally, Susan M. Majka
Journal: Journal of Clinical Investigation (2023)

Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic analyses. These studies link human and mouse MVPC-specific mTORC1 activation to decreased stemness, angiogenic potential, and disruption of p53 and Wnt pathways, with consequent loss of alveolar-capillary structure and function. Following mTOR activation, these MVPCs adapt a unique transcriptome signature and emerge as a venous subpopulation in the angiodiverse microvascular endothelial subclusters. Thus, our findings support a significant role for mTOR in the maintenance of MVPC function and microvascular niche homeostasis as well as a cell-based mechanism driving loss of tissue structure underlying lung aging and the development of emphysema.
High-dimensional immunophenotyping reveals immune cell aberrations in patients with undiagnosed inflammatory and autoimmune diseases
Authors: Alisa A. Mueller, Takanori Sasaki, Joshua W. Keegan, Jennifer P. Nguyen, Alec Griffith, Alice M. Horisberger, Thomas Licata, Elizabeth Fieg, Ye Cao, Mehreen Elahee, Kathryne E. Marks, Daimon P. Simmons, Lauren C. Briere, Laurel A. Cobban, J. Carl Pallais, Frances A. High, Melissa A. Walker, Jenny J. Linnoila, Jeffrey A. Sparks, V. Michael Holers, Karen H. Costenbader, David A. Sweetser, Joel B. Krier, Joseph Loscalzo, James A. Lederer, Deepak A. Rao
Journal: Journal of Clinical Investigation (2023)
Olympic Games during nationwide lockdown: sports injuries and illnesses, including COVID-19, at the Beijing 2022 Winter Olympics
Authors: Torbjørn Soligard, Debbie Palmer, Kathrin Steffen, Alexandre Dias Lopes, Natalia Grek, Xuan He, Yan Wang, Marie-Elaine Grant, Brett G Toresdahl, Matthias Gilgien, Richard Budgett, Lars Engebretsen
Journal: British Journal of Sports Medicine (2023)

The objective of this study is to describe the incidence of injuries and illnesses sustained during the Beijing Winter Olympic Games from 4 February 2022 to 20 February 2022.We recorded the daily number of athlete injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Beijing 2022 medical staff.In total, 2848 athletes (1276 women, 45%; 1572 men, 55%) from 91 NOCs were followed prospectively for the occurrence of injury and illness. NOC and Beijing 2022 medical staff reported 289 injuries and 109 illnesses, equalling 10.1 injuries and 3.8 illnesses per 100 athletes over the 17-day period. The injury incidence was highest in ski halfpipe (30%), ski big air (28%), snowboard slopestyle (23%) and ski slopestyle (22%), and lowest (1%-2%) in curling, alpine mixed team parallel slalom, Nordic combined and alpine super-G. The illness incidence was highest in ski aerials (10%), skeleton (8%), cross-country skiing (8%) and Nordic combined (7%). In the study period, COVID-19 affected 32 athletes, accounting for 29% of all illnesses affecting 1.1% of all athletes.Overall, 10% of the athletes incurred an injury and 4% an illness during the Beijing Winter Olympic Games. The incidence of illnesses overall, which was the lowest yet recorded in the Winter Olympic Games, and COVID-19 was mitigated through comprehensive countermeasures.
Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions
Authors: Vlad Ratziu, Marcus Hompesch, Mathieu Petitjean, Cindy Serdjebi, Janani S. Iyer, Anil V. Parwani, Dean Tai, Elisabetta Bugianesi, Kenneth Cusi, Scott L. Friedman, Eric Lawitz, Manuel Romero-Gómez, Detlef Schuppan, Rohit Loomba, Valérie Paradis, Cynthia Behling, Arun J. Sanyal
Journal: Journal of Hepatology (2023)
Significance of Crypt Atypia in Barrett’s Esophagus: A Clinical, Molecular, and Outcome Study
Authors: Helen H. Wang, Deepa T. Patil, Thomas G. Paulson, William M. Grady, Robert D. Odze
Journal: Clinical Gastroenterology and Hepatology (2023)

The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett's esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).
Prevalence of Barrett’s Esophagus and Esophageal Adenocarcinoma With and Without Gastroesophageal Reflux: A Systematic Review and Meta-analysis
Authors: Bibek Saha, Kornpong Vantanasiri, Babu P. Mohan, Rohit Goyal, Nikita Garg, Danielle Gerberi, John B. Kisiel, Siddharth Singh, Prasad G. Iyer
Journal: Clinical Gastroenterology and Hepatology (2023)
A microfluidic hemostatic diagnostics platform: Harnessing coagulation-induced adaptive-bubble behavioral perception
Authors: Longfei Chen, Le Yu, Ming Chen, Yantong Liu, Hongshan Xu, Fang Wang, Jiaomeng Zhu, Pengfu Tian, Kezhen Yi, Qian Zhang, Hui Xiao, Yongwei Duan, Wei Li, Linlu Ma, Fuling Zhou, Yanxiang Cheng, Long Bai, Fubing Wang, Xuan Xiao, Yimin Zhu, Yi Yang
Journal: Cell Reports Medicine (2023)

Clinical viscoelastic hemostatic assays, which have been used for decades, rely on measuring biomechanical responses to physical stimuli but face challenges related to high device and test cost, limited portability, and limited scalability.. Here, we report a differential pattern using self-induced adaptive-bubble behavioral perception to refresh it. The adaptive behaviors of bubble deformation during coagulation precisely describe the transformation of viscoelastic hemostatic properties, being free of the precise and complex physical devices. And the integrated bubble array chip allows microassays and enables multi-bubble tests with good reproducibility. Recognition of the developed bubble behaviors empowers automated and user-friendly diagnosis. In a prospective clinical study (clinical model development [n = 273]; clinical assay [n = 44]), we show that the diagnostic accuracies were 99.1% for key viscoelastic hemostatic assay indicators (reaction time [R], kinetics time [K], alpha angle [Angle], maximum amplitude [MA], lysis at 30 min [LY30]; n = 220) and 100% (n = 44) for hypercoagulation, healthy, and hypocoagulation diagnoses. This should provide fresh insight into existing paradigms and help more clinical needs.
Upper small intestine microbiome in obesity and related metabolic disorders: A new field of investigation
Authors: Emilie Steinbach, Davide Masi, Agnès Ribeiro, Patricia Serradas, Tiphaine Le Roy, Karine Clément
Journal: Metabolism (2023)

The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility.This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.
Dendritic Corneal Stromal Pigmentation: A Spillover of Nevus of Ota?
Authors: Somya Kumari, Abhishek Singh, Shikha Gupta
Journal: Ophthalmology (2023)

A 6-year-old girl presented (A) with congenital unilateral slate-grey hyperpigmentation of the eyelids, cheek, sclera, and (B) she had a brown, macular periumbilical dermal nevus. She had an intracorneal, brown, carpet-like lesion within the inferonasal corneal stroma, sparing the pupillary area. Her vision and intraocular pressure were within normal limits. Dendrite-like pigmentation fanned out intrastromally (C) within posterior stroma as on anterior-segment OCT (D), adjacent to scleral pigmentation, possibly representing scleral extension of Nevus of Ota. (Magnified version of Figure A-D is available online at www.aaojournal.org).
Full-thickness osteochondral defect repair using a biodegradable bilayered scaffold of porous zinc and chondroitin sulfate hydrogel
Authors: Fan Yang, Yageng Li, Lei Wang, Haodong Che, Xin Zhang, Holger Jahr, Luning Wang, Dong Jiang, Hongjie Huang, Jianquan Wang
Journal: Bioactive Materials (2023)

The regeneration of osteochondral tissue necessitates the re-establishment of a gradient owing to the unique characteristics and healing potential of the chondral and osseous phases. As the self-healing capacity of hyaline cartilage is limited, timely mechanical support during neo-cartilage formation is crucial to achieving optimal repair efficacy. In this study, we devised a biodegradable bilayered scaffold, comprising chondroitin sulfate (CS) hydrogel to regenerate chondral tissue and a porous pure zinc (Zn) scaffold for regeneration of the underlying bone as mechanical support for the cartilage layer. The photocured CS hydrogel possessed a compressive strength of 82 kPa, while the porous pure Zn scaffold exhibited a yield strength of 11 MPa and a stiffness of 0.8 GPa. Such mechanical properties are similar to values reported for cancellous bone. In vitro biological experiments demonstrated that the bilayered scaffold displayed favorable cytocompatibility and promoted chondrogenic and osteogenic differentiation of bone marrow stem cells. Upon implantation, the scaffold facilitated the simultaneous regeneration of bone and cartilage tissue in a porcine model, resulting in (i) a smoother cartilage surface, (ii) more hyaline-like cartilage, and (iii) a superior integration into the adjacent host tissue. Our bilayered scaffold exhibits significant potential for clinical application in osteochondral regeneration.
Actinic keratosis epidemiology: the good, the bad and the ugly
Authors: Luigi Naldi, Fortunato Cassalia
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Actinic keratosis epidemiology: the good, the bad and the ugly Get access Luigi Naldi, Luigi Naldi Conceptualization, Writing - original draft Department of Dermatology, Ospedale San Bortolo, Vicenza, ItalyCentro Studi GISED, Bergamo, Italy Correspondence: Luigi Naldi. Email: luiginaldibg@gmail.com https://orcid.org/0000-0002-3160-2835 Search for other works by this author on: Oxford Academic Google Scholar Fortunato Cassalia Fortunato Cassalia Data curation, Writing - review & editing Centro Studi GISED, Bergamo, ItalyDepartment of Dermatology, University of Padua, Padova, Italy https://orcid.org/0000-0002-5014-1122 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad395, https://doi.org/10.1093/bjd/ljad395 Published: 25 October 2023 Article history Received: 08 October 2023 Published: 25 October 2023 Corrected and typeset: 21 November 2023
Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder
Authors: Luis C. Farhat, José M. Flores, Victor J. Avila-Quintero, Guilherme V. Polanczyk, Andrea Cipriani, Toshi A. Furukawa, Michael H. Bloch, Samuele Cortese
Journal: JAMA Psychiatry (2023)

Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear.